Determination of the nature of the transduction, encoding, processing, and perception of acoustic signals is the major objective of this proposal. An interdisciplinary approach to such a problem is essential. Investigators trained in different disciplines combine their expertise and collaborative on four closely integrated projects to define and analyze the major events from acoustic activation of inner ear receptors to perception. The proposal's objectives are accomplished by experiments on: (1) the molecular and structural substrate underlying auditory processing and the active biochemical mechanisms in the cochlea; (2) the biochemical characteristics and control mechanisms that determine the molecular events involved in auditory transduction and its regulation; (3) electrophysiological features of hair cells and central auditory cells from cochlear nucleus to auditory cortex that determine encoding and processing; and (4) behavioral responses that reflect perceptual capacities of the auditory system for the identification, discrimination, and classification of these complex signals. These four projects are designed to yield information on the processing and perception of auditory signals at four levels of analysis, and data from each level of analysis impacts on the definition of experimental questions in the other projects. The Kresge Hearing Research Institute provides an ideal facility for this research with its multidisciplinary staff, appropriate laboratories, technical and support capabilities. The research team includes specialized personnel in anatomy, biochemistry, immunology, neuropharmacology, electrophysiology, bioengineering, and animal behavior. This group has a successful history of collaboration and provides a critical mass for the conceptualization and design of the proposed studies. This timely program continues to represent the core focus of the Institute and its faculty. The results will eventually give us a comprehensive view of the characteristics of the auditory system that underlie perception of biological signals. Clear and important clinical relevance of this program lies in the definition of specific events in auditory transduction, which will aid our understanding of possible causes of hearing loss. The analysis of the processing of complex signals will lead to improved designs for speech processing for cochlear prosthesis and hearing aids, and a clearer understanding of the basis and course of speech discrimination deficits with sensorineural hearing loss.